Project Summary Alzheimer's disease (AD) is the most common form of dementia, affecting roughly 5.5 million Americans, and is the sixth leading cause of death in the United States. Quantification of amyloid (A?) plaque burden with 18F and 11C- based Positron Emission Tomography (PET) imaging agents, based on high affinity A? aggregate-binding radionuclides shows promise for identifying individuals with increased risk of progressing to AD. However, PET imaging has several drawbacks including high cost, limited access, and poor spatial resolution. Furthermore, PET involves radiochemistry, which is both expensive and complex, thereby limiting distribution potential to specialized medical centers with radiochemistry capabilities. This Phase II project will seek to further develop ?ADx-Magnetic Resonance(MR)?, a targeted liposomal contrast agent that will be used in conjunction with 1.5T MR imaging systems, which are far more readily available than PET imaging systems, and much less expensive to use. The primary objectives of this Phase II grant is to gather safety/pharmacokinetic data in both small and large animals, and to transfer the synthesis process to a contract manufacturer in preparation for future GLP studies. ADx-MR has the potential to provide imaging of AD pathology at high resolution, and a significantly lower cost, with 5-10x more patient access points, than PET amyloid imaging. Coupled with the exceptional spatial resolution of MR Imaging, this agent enables the visualization of features at a voxel size of 100 m, a significant improvement over PET approaches with centimeter size voxels. To date, this novel, intravenously delivered A?-targeted liposome, ADx, has proven successful in in-vivo studies in three Alzheimer's mouse models. Alzeca has also performed dose ranging studies in mice and pilot PK studies in non-human primates. The goal of this project is therefore to advance ADx-MR, a liposomal T1-MR agent to qualify for a pre-IND meeting by establishing additional efficacy, safety, and scalability data.